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3120081 
Journal Article 
Autophagy is essential for ultrafine particle-induced inflammation and mucus hyperproduction in airway epithelium 
Chen, ZH; Wu, YF; Wang, PL; Wu, YP; Li, ZY; Zhao, Y; Zhou, JS; Zhu, C; Cao, C; Mao, YY; Xu, F; Wang, BB; Cormier, SA; Ying, SM; Li, W; Shen, HH 
2016 
Yes 
Autophagy
ISSN: 1554-8627 
12 
297-311 
English 
is supplemented by 3445245 : Supplementary materials
Environmental ultrafine particulate matter (PM) is capable of inducing airway injury, while the detailed molecular mechanisms remain largely unclear. Here, we demonstrate pivotal roles of autophagy in regulation of inflammation and mucus hyperproduction induced by PM containing environmentally persistent free radicals in human bronchial epithelial (HBE) cells and in mouse airways. PM was endocytosed by HBE cells and simultaneously triggered autophagosomes, which then engulfed the invading particles to form amphisomes and subsequent autolysosomes. Genetic blockage of autophagy markedly reduced PM-induced expression of inflammatory cytokines, e.g. IL8 and IL6, and MUC5AC in HBE cells. Mice with impaired autophagy due to knockdown of autophagy-related gene Becn1 or Lc3b displayed significantly reduced airway inflammation and mucus hyperproduction in response to PM exposure in vivo. Interference of the autophagic flux by lysosomal inhibition resulted in accumulated autophagosomes/amphisomes, and intriguingly, this process significantly aggravated the IL8 production through NFKB1, and markedly attenuated MUC5AC expression via activator protein 1. These data indicate that autophagy is required for PM-induced airway epithelial injury, and that inhibition of autophagy exerts therapeutic benefits for PM-induced airway inflammation and mucus hyperproduction, although they are differentially orchestrated by the autophagic flux. 
airway inflammation; autophagy; endocytosis; mucus hyperproduction; ultrafine particulate matter 
NAAQS
• ISA-PM (current)
     Considered
     In Scope
          Mode of action